Intercellular communication via the endo-lysosomal system: Translocation of granzymes through membrane barriers

Sarah Stewart, Michael D'Angelo, Phillip Bird

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Cytotoxic lymphocytes (CLs) are responsible for the clearance of virally infected or neoplastic cells. CLs possess specialised lysosome-related organelles called granules which contain the granzyme family of serine proteases and perforin. Granzymes may induce apoptosis in the target cell when delivered by the pore forming protein, perforin. Here we follow the perforin-granzyme pathway from synthesis and storage in the granule, to exocytosis and finally delivery into the target cell. This review focuses on the controversial subject of perforin-mediated translocation of granzymes into the target cell cytoplasm It remains unclear whether this occurs at the cell surface with granzymes moving through a perforin pore in the plasma membrane, or if it involves internalisation of perforin and granzymes and subsequent release from an endocytic compartment. The latter mechanism would represent an example of cross talk between the endo-lysosomal pathways of individual cells. Proteolysis 50years after the discovery of lysosome.
Original languageEnglish
Pages (from-to)59 - 67
Number of pages9
JournalBBA Proteins and Proteomics
Volume1824
Issue number1
DOIs
Publication statusPublished - 2012

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